Amyloid-Beta Peptide Is Toxic to Neurons In Vivo via Indirect Mechanisms

Abstract

We have studied the neurotoxicity of amyloid-beta (Aβ) after a single unilateral intravitreal injection. Within the retina apoptotic cells were seen throughout the photoreceptor layer and the inner nuclear layer but not in the ganglion cell layer at 48 h after injection of Aβ1-42 compared to vehicle control and control peptide. At 5 months, there was a significant reduction in total cell numbers in the ganglion cell layer in Nissl stained retinas. There was glial cell dysfunction with upregulation of glial fibrillary acidic protein and a reduction in the expression of Müller cell associated proteins in the injected retinas. These results suggest an indirect cytotoxic effect of Aβ on retinal neurons and an important role for dysfunction of Müller glia in mediating Aβ neurotoxicity.

Keywords

• amyloid-beta
• neurotoxicity
• retinal neurons
• Müller cells
• glial dysfunction
• neurodegeneration